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Evolocumab (Repatha) for Cardiovascular Event Prevention – Add on Therapy

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Evolocumab (Repatha) for Cardiovascular Event Prevention – Add on Therapy October Horizon Scanning Research & 2016 Intelligence Centre Evolocumab (Repatha) for cardiovascular event prevention – add on therapy NIHR HSRIC ID: 12592 Lay summary Evolocumab is a drug that may prevent cardiovascular events, such as heart attack or stroke, by reducing cholesterol. These diseases are the main cause of death in the UK, accounting for over a quarter of deaths each year. Evolocumab is given via an injection in combination with another drug (usually a statin) and changes to diet to lower cholesterol. If evolocumab can prevent cardiovascular events, it may help reduce deaths, illness and NHS costs caused by these diseases. However, the effect for evolocumab on death and disease relating to cardiovascular events has not yet been determined. This briefing is based on information available at the time of research and a limited literature search. It is not intended to be a definitive statement on the safety, efficacy or effectiveness of the health technology covered and should not be used for commercial purposes or commissioning without additional information. This briefing presents independent research funded by the National Institute for Health Research (NIHR). The views expressed are those of the author and not necessarily those of the NHS, the NIHR or the Department of Health. Horizon Scanning Research & Intelligence Centre University of Birmingham [email protected] www.hsric.nihr.ac.uk @OfficialNHSC Horizon Scanning Research & Intelligence Centre TARGET GROUP • Cardiovascular event prevention: in adults with history of clinically evident cardiovascular disease and additional characteristics that place them at higher cardiovascular risk – in combination with statins, with or without other lipid lowering therapies. TECHNOLOGY DESCRIPTION Evolocumab (Repatha; AMG-145) is a fully humanised monoclonal antibody targeted to proprotein convertase subtilisin/kexin type 9 (PCSK9). PCSK9 is a negative regulator of low- density lipoprotein (LDL) receptors in the liver, and reduces the ability of the liver to remove LDL-cholesterol (LDL-C) from the blood. Evolocumab prevents the degradation of LDL receptors regulated by PCSK9, thereby increasing the expression of LDL receptors on the surface of liver cells. PCSK9 inhibitors reduce LDL-C levels via an alternative mechanism to statins, and therefore offer potential to be used as an add on therapy when statins or other lipid-lowering therapies do not reduce LDL-C by a sufficient margin1. Evolocumab is administered by subcutaneous (SC) injection via a 140mg prefilled auto- injector pen2. In the phase III clinical trial evolocumab is administered at 140mg every two weeks or 420mg every month according to patient preference (or matching placebo injections)3. Evolocumab is currently licensed in the EU for adults with homozygous familial hypercholesterolaemia in combination with other lipid lowering therapies, and primary hypercholesterolaemia (heterozygous familial and non-familial) or mixed dyslipidaemia in combination with a statin or a statin and other lipid lowering therapies (or alone for patients with statin intolerance or contraindications). The most commonly reported adverse effects include: influenza, nasopharyngitis, upper respiratory tract infection, nausea, back pain, arthralgia, rash and injection site reactions4. Evolocumab is also in phase III trials in patients with clinically evident cardiovascular disease, subjects with type 2 diabetes mellitus with hypercholesterolaemia/mixed dyslipidaemia, and paediatric subjects with genetic LDL disordersa. INNOVATION and/or ADVANTAGES If licensed, evolocumab will represent a new treatment option for the prevention of cardiovascular events that can be used in addition to statins and/or other lipid-lowering therapies in patients at increased risk of cardiovascular morbidity and mortality. DEVELOPER Amgen Limited. a Evolocumab is currently under additional clinical monitoring for such new indications. 2 Horizon Scanning Research & Intelligence Centre AVAILABILITY, LAUNCH OR MARKETING In phase III clinical trials. PATIENT GROUP BACKGROUND There are many factors associated with increased cardiovascular disease risk. The key behavioural risk factors include smoking, physically inactive lifestyles, poor diet, obesity and alcohol consumption. Medical risk factors include high blood pressure, high blood cholesterol and diabetes. Further risk factors include exposure to air pollution, increasing age, gender, family history and ethnicity5. The accumulation of LDL-C in the intima (inner lining) of arteries and associated inflammatory reactions gradually lead to the formation of atherosclerotic plaques within the arterial tree. Atherosclerotic plaques obstruct blood flow and reduce oxygen supply which in turn can lead to cardiovascular events, such as ischemic stroke and myocardial infarction6. CLINICAL NEED and BURDEN OF DISEASE Diseases of the heart and circulatory system (including peripheral vascular disease and stroke) are the main cause of death in the UK, accounting for over a quarter of UK deaths each year (160,000)5. Healthcare costs relating to these diseases are estimated to be up to £11 billion each year, and costs to the UK economy are estimated to be over £15 billion per 5 year . In 2015, there were an estimated seven million people living with heart and circulatory 5 system diseases in the UK . Primary non-familial hypercholesterolaemia affects about 4% of the adult population, or approximately 1.5 million people in England. Of these, an estimated 600,000 are diagnosed. It is estimated that 460,000 are actively having treatment for primary non-familial hypercholesterolaemia. Of these it is estimated that 12,088 may have LDL-C levels that are not adequately controlled by statins and/or ezetimibe7. The prevalence of familial hypercholesterolaemia in the UK is about 1 in 500 (around 13,000 adults in England), but over 85% of people with the disease are thought to remain 7 undiagnosed . It is unclear what percentage of people with diagnosed cardiovascular disease also have familial hyperlipidaemia or mixed dyslipidaemia. PATIENT PATHWAY RELEVANT GUIDANCE NICE Guidance • NICE technology appraisal. Evolocumab for treating primary hypercholesterolaemia and mixed dyslipidaemia (TA394). June 2016. • NICE technology appraisal. Alirocumab for treating primary hypercholesterolaemia and mixed dyslipidaemia (TA393). June 2016. • NICE technology appraisal. Ticagrelor for the treatment of acute coronary syndromes (TA236). October 2011. 3 Horizon Scanning Research & Intelligence Centre • NICE technology appraisal. Statins for the prevention of cardiovascular events (TA94). November 2008. • NICE clinical guideline. Cardiovascular disease: risk assessment and reduction, including lipid modification (CG181). July 2014. • NICE clinical guideline. Myocardial infarction: cardiac rehabilitation and prevention of further MI (CG172). November 2013. • NICE clinical guideline. Management of stable angina (CG126). July 2011. • NICE clinical guideline. Hypertension in adults: diagnosis and management (CG127). August 2011. • NICE clinical guideline. Familial hypercholesterolaemia: identification and management (CG71). August 2008. • NICE clinical guideline. Secondary prevention in primary and secondary care for patients following a myocardial infarction (CG48). May 2007. • NICE quality standard. Cardiovascular risk assessment and lipid modification (QS100). September 2015. • NICE quality standard. Familial hypercholesterolaemia (QS41). August 2013. • NICE quality standard. Stable angina (QS21). August 2012. • NICE public health guidance. Guidance on the prevention of cardiovascular disease at the population level (PH25). June 2010. • NICE public health guidance. Cardiovascular disease: identifying and supporting people most at risk of dying early (PH15). September 2008. NHS England Policies and Guidance • NHS England. 2013/14 NHS standard contract for cardiology: inherited cardiac conditions (All ages). A09/S/c. Other Guidance • European Society of Cardiology. Dyslipidaemias. 20168. • European Society of Cardiology. Cardiovascular disease prevention in clinical practice. 20169. • Scottish Intercollegiate Guidelines Network. Acute Coronary Syndromes. (148). 201610. • European Society of Cardiology. Acute Coronary Syndromes (ACS) in patients presenting without persistent ST-segment elevation (Management of). 201511. • DH Cardiovascular Team. Cardiovascular Diseases Outcome Strategy. 201312. • European Society of Cardiology and the European Atherosclerosis Society. ESC/EAS guidelines for the management of dyslipidaemias. 201113. • NHS Healthcheck programme. 200914. • Scottish Intercollegiate Guidelines Network. Risk estimation and the prevention of cardiovascular disease (97). 200715. • World Health Organisation. Prevention of cardiovascular disease: pocket guidelines for assessment and management of cardiovascular risk. 200716. 4 Horizon Scanning Research & Intelligence Centre CURRENT TREATMENT OPTIONS To prevent recurrent cardiovascular events, individual patients’ cardiovascular risk must be reduced. This includes lifestyle changes such as dietary modification, smoking cessation, and exercise. Current pharmacological treatment options for the prevention of cardiovascular events in high-risk patients include17,18: • Lipid lowering therapies, which include statins (simvastatin, pravastatin, fluvastatin, atorvastatin, rosuvastatin), fibrates (bezafibrate, ezetimibe, ciprofibrate, fenofibrate and gemfibrozil). Nicotinic acid and anion exchange
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